Maintenance of the Expression of c-FLIPL by Hsp70 to Resist Licochalcone A-Induced Anti-Colorectal Cancer Effect through ERK-Mediated Autophagy Induction.

BACKGROUND: The mortality rate of colorectal cancer (CRC) ranks second worldwide. Previous research had indicated that licochalcone A (LA) was a flavonoid in licorice with diverse anticancer effects. We explored the underlying mechanisms of LA-triggered anticancer activity in CRC. METHODS: Thiazolyl Blue (MTT) experiment and EdU staining were utilized to evaluate cell proliferation. Meanwhile, cells were stained by Annexin V/PI to investigate apoptosis through flow cytometry assay. Moreover, expressions of proteins were detected by immunoblotting, and the level of related mRNA was investigated using real-time quantitative PCR. RESULTS: LA selectively suppressed the proliferation and triggered apoptosis of CRC cells. Strikingly, LA induced cytoprotective autophagic activities since the suppression of autophagy significantly strengthened LA-induced cytotoxicity and FLICE inhibitory protein (c-FLIPL) degradation, meanwhile reversing LA-mediated heat shock protein 70 (Hsp70) upregulation. Moreover, autophagy-mediated Hsp70 upregulation resisted LA-induced anticancer effects since the suppression of Hsp70 strengthened LA-triggered cytotoxicity and c-FLIPL degradation. Furthermore, LA greatly activated extracellular signal-regulated protein kinases (ERK) and p38. However, blocking of ERK, but not p38, significantly boosted LA-triggered cell death and c-FLIPL downregulation. Suppression of ERK also reversed LA-mediated autophagic induction. CONCLUSIONS: LA increased Hsp70 expression depending on ERK-mediated autophagy, which protected CRC cells from LA-induced anticancer activities.

Revealing the mechanisms of alkali-based magnetic nanosheets enhanced hydrogen production from dark fermentation: Comparison between mesophilic and thermophilic conditions.

In the present study, a dark fermentation system inoculated with mixed culture bacteria (MCB) was developed using prepared alkali-based magnetic nanosheets (AMNSs) to facilitate biohydrogen (BioH2) production. The highest BioH2 yields of 232.8 ± 8.5 and 150.3 ± 4.8 mL/g glucose were observed at 100 (mesophilic condition) and 400 (thermophilic condition) mg/L AMNSs groups, which were 65.4% and 43.3%, respectively, above the 0 mg/L AMNSs group. The fermentation pathway revealed that AMNSs enhanced the butyrate-type metabolic pathway and the corresponding nicotinamide adenine dinucleotides (NADHand NAD+) ratio, and hydrogenase activity was enhanced in mesophilic fermentation. The interaction of AMNSs and MCB suggested that AMNSs could assist in electron transfer and that the released metal elements might be responsible for elevated hydrogenase activity. AMNSs also promoted the evolution of the dominant microbial community and altered the content of extracellular polymers, leading to increased production of BioH2.

Chaperone Spy Protects Outer Membrane Proteins from Folding Stress via Dynamic Complex Formation.

Gram-negative bacteria have a multicomponent and constitutively active periplasmic chaperone system to ensure the quality control of their outer membrane proteins (OMPs). Recently, OMPs have been identified as a new class of vulnerable targets for antibiotic development, and therefore a comprehensive understanding of OMP quality control network components will be critical for discovering antimicrobials. Here, we demonstrate that the periplasmic chaperone Spy protects certain OMPs against protein-unfolding stress and can functionally compensate for other periplasmic chaperones, namely Skp and FkpA, in the Escherichia coli K-12 MG1655 strain. After extensive in vivo genetic experiments for functional characterization of Spy, we use nuclear magnetic resonance and circular dichroism spectroscopy to elucidate the mechanism by which Spy binds and folds two different OMPs. Along with holding OMP substrates in a dynamic conformational ensemble, Spy binding enables OmpX to form a partially folded ß-strand secondary structure. The bound OMP experiences temperature-dependent conformational exchange within the chaperone, pointing to a multitude of local dynamics. Our findings thus deepen the understanding of functional compensation among periplasmic chaperones during OMP biogenesis and will promote the development of innovative antimicrobials against pathogenic Gram-negative bacteria. IMPORTANCE Outer membrane proteins (OMPs) play critical roles in bacterial pathogenicity and provide a new niche for antibiotic development. A comprehensive understanding of the OMP quality control network will strongly impact antimicrobial discovery. Here, we systematically demonstrate that the periplasmic chaperone Spy has a role in maintaining the homeostasis of certain OMPs. Remarkably, Spy utilizes a unique chaperone mechanism to bind OmpX and allows it to form a partially folded ß-strand secondary structure in a dynamic exchange of conformations. This mechanism differs from that of other E. coli periplasmic chaperones such as Skp and SurA, both of which maintain OMPs in disordered conformations. Our study thus deepens the understanding of the complex OMP quality control system and highlights the differences in the mechanisms of ATP-independent chaperones.

Quality of life in adolescent patients with idiopathic scoliosis after brace treatment: A meta-analysis.

BACKGROUND: Whether brace-treated adolescents with idiopathic scoliosis (AIS) have improved quality of life (QoL) is still unknown. Thus, we conducted a meta-analysis to compare the QoL of brace-treated AIS patients with untreated AIS patients. The pain, self-image/appearance, mental health, function/activity, satisfaction with management, total score without satisfaction, and total score of patients were used to measure the QoL after the intervention. METHODS: Multiple electronic databases including PubMed, Web of Science, and Embase were searched for all years up to June 30, 2016. Articles in English that used the Scoliosis Research Society-22 (SRS-22) or a modified version of the SRS-22 questionnaire to evaluate the QoL differences between brace-treated AIS patients and untreated AIS patients were included in the meta-analysis. The Newcastle-Ottawa Scale was used in the quality of literature evaluation. The pooled standardized mean difference (SMD) with its corresponding 95% confidence interval (CI) for each parameter was computed. Egger test and Begg test were used to test for publication bias. RESULTS: The SRS-22 or a modified SRS-22 questionnaire was used to evaluate the QoL after surgery. There was no significant difference in pain (SMD = 0.123, 95% CI: -0.101 to 0.347, P = .282), self-image/appearance (SMD = 0.108, 95% CI: -0.116 to 0.332, P = .334), mental health (SMD = 0.031, 95% CI: -0.130 to 0.201, P = .365), function/activity (SMD = 0.202, 95% CI: -0.022 to 0.425, P = .077), and total score without satisfaction (SMD = 0.123, 95% CI: -0.232 to 0.478, P = .497) between the untreated (observation) and brace-treated AIS patients, whereas a significant difference was observed in satisfaction with management (SMD = 0.393, 95% CI: 0.127-0.659, P = .004) and total score (SMD = 0.312, 95% CI: 0.054-0.571, P = .018) between the 2 groups. CONCLUSION: Our meta-analysis indicated that brace-treated AIS patients had a higher QoL. However, further analysis could not be performed because of insufficient data, such that we were unable to make subgroup analysis of QoL for different types of AIS and the therapeutic methods chosen by brace-treated AIS patients.

microRNA Profiling of Amniotic Fluid: Evidence of Synergy of microRNAs in Fetal Development.

Amniotic fluid (AF) continuously exchanges molecules with the fetus, playing critical roles in fetal development especially via its complex components. Among these components, microRNAs are thought to be transferred between cells loaded in microvesicles. However, the functions of AF microRNAs remain unknown. To date, few studies have examined microRNAs in amniotic fluid. In this study, we employed miRCURY Locked Nucleotide Acid arrays to profile the dynamic expression of microRNAs in AF from mice on embryonic days E13, E15, and E17. At these times, 233 microRNAs were differentially expressed (p< 0.01), accounting for 23% of the total Mus musculus microRNAs. These differentially-expressed microRNAs were divided into two distinct groups based on their expression patterns. Gene ontology analysis showed that the intersectional target genes of these differentially-expressed microRNAs were mainly distributed in synapse, synaptosome, cell projection, and cytoskeleton. Pathway analysis revealed that the target genes of the two groups of microRNAs were synergistically enriched in axon guidance, focal adhesion, and MAPK signaling pathways. MicroRNA-mRNA network analysis and gene- mapping showed that these microRNAs synergistically regulated cell motility, cell proliferation and differentiation, and especially the axon guidance process. Cancer pathways associated with growth and proliferation were also enriched in AF. Taken together, the results of this study are the first to show the functions of microRNAs in AF during fetal development, providing novel insights into interpreting the roles of AF microRNAs in fetal development.